Management of Dermatomyositis

Introduction

I. Initial Assessment Before Starting Treatment (1 mark)

• Comprehensive history, physical examination (including pelvic exam in women)
• CBC, LFT, RFT, urinalysis, stool occult blood
• CT chest/abdomen/pelvis; colonoscopy
• PET scan in selected cases
• Age/sex/ethnicity-appropriate screening (mammogram, Pap smear, nasopharyngoscopy in Asians for NPC)
• Autoantibody panel (anti-TIF1-γ / anti-NXP-2 = high malignancy risk; anti-Jo-1 = ILD risk; anti-MDA5 = rapidly progressive ILD)

II. General Measures (0.5 mark)

• Photoprotection: Broad-spectrum sunscreen SPF ≥30 (with UVA cover) applied daily; sun-protective clothing, hats. Critical because DM is photosensitive and UV exacerbates both skin and muscle disease.
• Rest during active disease with graded physical therapy and physiotherapy once muscle inflammation is controlled, to prevent contractures and improve strength.
• Osteoporosis prophylaxis: Calcium + Vitamin D supplementation; bisphosphonate if long-term corticosteroids are anticipated.
• Monitoring: Repeat CK/aldolase every 2–3 months to guide therapy.

III. Treatment of Muscle Disease (Myositis) (3 marks)

First-Line: Systemic Corticosteroids

• Dose: 1 mg/kg/day (max 60–80 mg/day) orally; continued until muscle strength improves and enzymes normalize
• CK and AST/ALT return to normal as remission occurs
• Taper: Reduce to 0.5 mg/kg/day (single morning dose) by 6–8 months
• Disease under control rapidly in 2–4 weeks if CK mildly elevated; if CK >1000 U/L, use IV pulse methylprednisolone (1 g/day × 3 days) plus early steroid-sparing agent
• Monitoring for steroid toxicity: Hyperglycemia, hypertension, GI ulceration, adrenal suppression, cataracts, avascular necrosis

Second-Line: Steroid-Sparing Agents (Immunosuppressants)

IV. Treatment of Skin Disease (2 marks)

Topical Therapies

• Topical corticosteroids (mid-to-high potency): for limited cutaneous disease, pruritus
• Topical tacrolimus (0.1%): Steroid-sparing for facial lesions; calcineurin inhibitor

Systemic Therapies for Cutaneous DM

• Hydroxychloroquine: 5 mg/kg/day divided (up to 200 mg BD) — standard of care for skin lesions; note higher rate of cutaneous drug eruptions in DM (~25%) compared to SLE. If inadequate, add quinacrine 100 mg/day (triple therapy with chloroquine + quinacrine also used)
• IVIG (intravenous immunoglobulin): 2 g/kg/month (0.5–1 g/kg/day × 2 days/month) — beneficial particularly for skin disease; Level 1 evidence; also effective in refractory anti-MDA5 disease with rapidly progressive ILD. Risks: thromboembolism (DVT, PE, MI, stroke) — consider concomitant aspirin
• Dapsone: Useful for cutaneous DM (case reports and series)
• Low-dose methotrexate: Effective for recalcitrant skin disease

V. Treatment of Refractory/Severe Disease (2 marks)

• Rituximab: Anti-CD20 monoclonal antibody; 375 mg/m² × 4 weekly doses or 1 g × 2 doses; improves muscle disease; less effective for skin disease; promising in refractory juvenile DM
• Tacrolimus (oral): Particularly effective in severe refractory disease; also useful in anti-MDA5 DM with ILD
• Cyclosporine: 2.5–5 mg/kg/day; used in severe/refractory cases
• Cyclophosphamide: Reserved for life-threatening ILD or vasculitis
• JAK inhibitors (Tofacitinib 5–10 mg/day; Ruxolitinib): Dramatic benefit reported in refractory DM; rationale — type I IFN/JAK-STAT pathway is central to DM pathogenesis; particularly for refractory cutaneous disease
• Infliximab / Anti-TNF-α: Rapidly effective for myositis in some patients; use with caution — anti-TNF therapy can itself induce DM and cause flares
• Leflunomide: Adjuvant immunomodulatory therapy (used in RA); effective in DM
• Anakinra, tocilizumab, abatacept: Emerging biologics in small series

VI. Treatment of Complications (1 mark)

Calcinosis Cutis

• Diltiazem: Most commonly used
• Aluminum hydroxide, bisphosphonates (alendronate), probenecid, colchicine, low-dose warfarin, sodium thiosulfate
• Surgical excision: For large, painful, or functionally limiting deposits
• Prevention: Early, aggressive therapy in juvenile DM reduces calcinosis risk

Interstitial Lung Disease (ILD)

• MMF preferred steroid-sparer (antifibrotic effect)
• Cyclophosphamide or rituximab for rapidly progressive ILD (esp. anti-MDA5 DM)
• Pirfenidone/nintedanib under investigation

Dysphagia

• Nasogastric/PEG feeding in severe cases
• IVIG, IV methylprednisolone for acute pharyngeal myositis

VII. Management in Special Situations (0.5 mark)

Juvenile DM

• IV/oral pulse methylprednisolone for acute management
• Methotrexate or IVIG may be equally effective, possibly avoiding corticosteroids
• Rituximab promising in refractory cases
• Early aggressive treatment reduces calcinosis

Pregnancy

• Topical corticosteroids and topical calcineurin inhibitors are first-line
• Systemic corticosteroids, hydroxychloroquine, and azathioprine are acceptable when necessary
• Avoid methotrexate, MMF, cyclophosphamide (teratogenic)

Cancer-Associated DM

• Treat underlying malignancy — DM course does not always parallel the malignancy
• Use immunosuppression strategies similar to non-paraneoplastic DM (corticosteroids, methotrexate, azathioprine, MMF, IVIG, rituximab)

VIII. Monitoring and Follow-Up (implied)

• CK/aldolase every 2–3 months
• Annual malignancy surveillance (risk remains elevated >5 years)
• DEXA scan for osteoporosis
• PFTs annually (ILD monitoring)
• Ophthalmologic review for hydroxychloroquine toxicity (annual after 5 years)

Summary Table: Therapeutic Ladder for DM

Prognosis Note

A) Porokeratosis

Definition

Genetics and Pathogenesis

• Most variants are inherited as autosomal dominant traits (with the exception of CDAGS syndrome — autosomal recessive)
• Mutations in the mevalonate/cholesterol biosynthetic pathway (e.g., PMVK, MVK, MVD, FDPS genes) underlie several forms
• Precipitating factors: UV radiation, immunosuppression (post-transplant, HIV, immunosuppressive drugs), radiation therapy — all can trigger or exacerbate the condition
• Clonal proliferation of abnormal keratinocytes is the underlying mechanism

Clinical Variants (at least 6 recognized)

Histopathology (the cornerstone)

• A thin column of parakeratotic cells running obliquely through the stratum corneum at the edge of the lesion
• The granular layer is absent or markedly reduced beneath the cornoid lamella (present elsewhere)
• Underlying keratinocytes are edematous with shrunken nuclei
• Dermal lymphocytic infiltrate may be present
• Central epidermis may be normal, atrophic, or hyperplastic
• ⚠️ The cornoid lamella is characteristic but not pathognomonic — also seen in viral warts, some ichthyoses, and nevoid hyperkeratoses

Malignant Transformation

• Occurs in 7–11% of cases
• Risk order: Linear > Mibelli > PPPD > DSAP (punctate — NO malignancy)
• Tumors: SCC most common; also Bowen disease, BCC
• Markers of increased risk: giant/large lesions, immunosuppression, chronic UV exposure

Treatment

• 5-Fluorouracil cream — effective for individual lesions; may need occlusion
• Imiquimod 5% — immunomodulatory
• Calcipotriol (Vitamin D3 analogue) — useful, especially DSAP
• Topical retinoids (tazarotene)
• Keratolytics (salicylic acid, α-hydroxy acids)
• Topical corticosteroids
• Tacrolimus 0.1% — particularly for linear porokeratosis

• Cryotherapy (most common destructive approach)
• CO₂ laser ablation (must reach mid-dermis to prevent recurrence)
• Nd:YAG laser, pulsed dye laser
• Electrodesiccation + curettage, dermabrasion
• Surgical excision (for linear/giant lesions)

• Oral retinoids — most reproducible results; recurrence upon cessation
• Oral retinoids + topical 5-FU combination for refractory DSAP

B) Tinea Imbricata

Definition and Synonyms

Epidemiology / Geographic Distribution

• Strictly endemic to:
  • Southwest Polynesia (Tokelau Islands — hence the name)
  • Melanesia (Papua New Guinea, Solomon Islands)
  • Southeast Asia (Malaysia, Philippines, Indonesia)
  • Central America (Mexico, parts of South America)
  • India (tribal populations)
• Confined to humid tropical environments
• Affects all ages and both sexes; children often acquire it from mothers
• Genetic susceptibility: HLA-linked; certain racial groups are highly susceptible; Caucasians are relatively resistant even after exposure

Etiology

• Causative organism: Trichophyton concentricum — an anthropophilic dermatophyte
• Exclusively causes tinea imbricata; found nowhere outside endemic areas
• Similar concentric patterns may rarely be produced by T. mentagrophytes and T. tonsurans but are atypical

Clinical Features

Morphology

• Begins as one or several small, rounded macules on the trunk and arms
• The macule splits in the center → large, flaky scales attached at the periphery with free edges pointing inward
• A new brownish macule forms in the center, undergoes the same splitting-and-extension cycle
• This repeats to produce:
  • Concentric rings of scales → characteristic "target-like" or "fingerprint" pattern
  • Polycyclic overlapping borders — the scales overlap each other like shingles/tiles
  • Extensive patches covering large body surface areas
• Erythema is typically minimal or absent
• Entire body surface may be involved except scalp, palms, soles, and mucosal surfaces (usually spared)

Subjective

• Pruritus variable; often mild
• Condition is chronic and lifelong in endemic populations

Diagnosis

• Clinical appearance in an endemic region is usually diagnostic
• KOH microscopy: Interlacing septate mycelial filaments that branch dichotomously; polyhedral spores also present
• Culture: On Sabouraud dextrose agar — slow-growing, waxy, folded, cream to buff colored colonies

Differential Diagnosis

• Psoriasis (scales, but plaque morphology different)
• Pityriasis rosea (herald patch + Christmas tree pattern)
• Ichthyosis linearis circumflexa (migratory, scaly plaques with double-edged scale)
• Erythrokeratoderma variabilis

Treatment

• Terbinafine — drug of choice; most effective; 250 mg/day for 2–4 weeks; excellent response rates
• Griseofulvin — effective but high recurrence rate; long courses required
• Itraconazole — also used; 200 mg/day for 2–4 weeks
• Topical antifungals are generally inadequate due to the extent of involvement but may be adjunctive
• ⚠️ Recurrence is common in endemic areas due to re-exposure; some patients require repeated or prolonged courses

C) Pellagra (PEM — Pellagra as nutritional dermatosis)

Note on "PEM": In dermatology PG exams, PEM under nutritional skin diseases commonly refers to Pellagra (niacin/tryptophan deficiency) and/or Protein-Energy Malnutrition (kwashiorkor/marasmus). Both are covered here.

PART I: PELLAGRA (Niacin Deficiency)

Definition

Etiology / Causes

• Dietary: Corn/maize-based diet (corn is low in niacin and bound niacin is not bioavailable); millet, sorghum
• Alcoholism — commonest cause in developed countries
• Drugs: Isoniazid (most common drug cause), azathioprine, 6-MP, 5-FU, ethionamide, pyrazinamide, anticonvulsants (phenobarbital, hydantoin, carbamazepine)
• Metabolic disorders:
  • Carcinoid tumors — divert tryptophan → serotonin
  • Hartnup disease — impaired intestinal/renal tryptophan absorption
  • GI disorders (Crohn disease, GI surgery, malabsorption)
• Pyridoxine (B6) deficiency (co-factor for tryptophan → niacin conversion)
• Prolonged IV therapy, anorexia nervosa, restrictive diets

Clinical Features

• Photosensitive eruption — worsens in spring/summer; symmetric on sun-exposed sites:
  • Casal necklace: broad, well-demarcated dermatitis around the neck (V of chest)
  • Extensor forearms, dorsa of hands, face (butterfly distribution on face)
• Initially: erythema and edema resembling sunburn; burning and pruritus
• "Wet pellagra": vesicles and bullae in severe cases
• Chronic: thickening, hyperpigmentation, scaling → mahogany/copper hue
• Late: dry, atrophic, parchment-like, "glassy" skin
• Nose: Dull erythema of bridge with fine yellow powdery scales over follicular orifices ("sulfur flakes")
• Pellagrous skin takes 4× longer to recover from acute phototoxic injury than normal sunburn

Histopathology

• Pallor and vacuolar changes of keratinocytes in a band in upper stratum malpighii just below the granular layer (pathognomonic-like finding)
• Granular layer attenuated; in severe cases → intraepidermal cleft (correlating with blistering)
• Depletion of Langerhans cells in the skin

Diagnosis

• Clinical features ± dietary history
• Laboratory: urine N-methylnicotinamide/2-pyridone levels (decreased)
• Response to niacin supplementation confirms diagnosis

Treatment

• Nicotinamide 100 mg three times daily for several weeks (nicotinamide preferred over nicotinic acid — avoids flushing)
• Correct underlying cause (diet, alcohol, offending drug)
• Replace fluid and electrolytes (for diarrhea)
• If GI involvement → initial IV supplementation
• Animal proteins, eggs, milk, vegetables
• Within 24 hours of niacin therapy, skin lesions begin to resolve — this confirms the diagnosis
• Treat underlying alcoholism, carcinoid, or Hartnup disease

PART II: PROTEIN-ENERGY MALNUTRITION (Kwashiorkor)

Classification

• Marasmus: Deficiency of both protein + calories; <60% ideal body weight; NO edema or dermatosis; dry, wrinkled, loose skin with loss of subcutaneous fat; loss of buccal fat pad
• Kwashiorkor: Protein deficiency with relatively adequate calories; 60–80% IBW; edema + hypoproteinemia
• Marasmic kwashiorkor: Features of both; <60% IBW + edema

Kwashiorkor — Skin and Hair Features

• Hypopigmentation — reddish-yellow to gray or white
• Dry, lusterless; curly hair becomes soft and straight
• Flag sign: alternating bands of pale and dark hair along a single strand (indicating alternating periods of poor and good nutrition)
• Soft, thin nails

• Hypopigmented patches on dark skin; erythematous/purple on lighter skin
• First appear in areas of friction/pressure: flexures, groin, buttocks, elbows
• Hyperpigmented patches with slightly raised edges progressing to peeling desquamation
• Descriptive signs: "flaky paint" / "crazy pavement" / "cracked skin" / "enamel paint" / "mosaic skin" dermatosis
• In severe cases: peeling leaves pale ulcerated hypopigmented areas with hyperpigmented borders
• Pitting edema (can mask true growth failure)
• Potbelly (hepatomegaly from fatty liver)
• Concomitant zinc deficiency → acrodermatitis enteropathica-like picture

Treatment of Kwashiorkor

• Gradual refeeding — start with low-protein diet, increase slowly (risk of refeeding syndrome)
• High-quality protein: milk, eggs, animal proteins
• Correct electrolyte imbalance, treat infections
• Micronutrient supplementation: zinc, vitamin A, B complex, iron (after stabilization)
• UNICEF F-75 → F-100 therapeutic feeding protocol in severe acute malnutrition
• Treat underlying causes (food allergy, dietary restriction, GI disease)

D) Alopecia Mucinosa (Follicular Mucinosis)

Definition

Classification

Etiology and Pathogenesis

• Unknown in primary form
• CD4+ T-cell mediated folliculotropic inflammatory process
• Secondary follicular mucinosis arises from folliculotropic mycosis fungoides (FMF) — a variant of CTCL
• Mucin (glycosaminoglycan) accumulates due to altered proteoglycan metabolism in the pilosebaceous unit

Clinical Features

Primary Alopecia Mucinosa

• Well-demarcated, indurated erythematous or skin-colored patches/plaques causing scarring or non-scarring alopecia
• Head and neck most commonly involved
• Scalp lesions: well-defined areas of hair loss (2–6 cm diameter), often with inflammation
• Grouped erythematous follicular papules within hairless patches (hallmark)
• Follicular cysts, follicular hyperkeratosis
• Alopecia of eyebrows may occur
• Diffuse hair loss occasionally

Secondary (Folliculotropic MF-associated)

• Larger plaques, often on head/neck
• May show acneiform lesions, comedone-like follicular plugs
• Pruritus may be severe
• More extensive and persistent than idiopathic form
• Risk of progression to Sézary syndrome

Trichoscopy

• Multiple enlarged follicular openings filled with keratotic material
• Loss of follicular pattern in affected areas

Histopathology (key points)

• Mucin deposition (pale, stringy, basophilic material on H&E; positive with Alcian blue and colloidal iron stains) in the outer root sheath and sebaceous glands
• In early lesions: mucin in outer root sheath
• In advanced lesions: replacement of the entire pilosebaceous unit by pools of mucin
• Spongiosis of the follicular epithelium
• Perifollicular lymphocytic infiltrate (may include eosinophils)
• ⚠️ Evidence of lymphocyte atypia and/or monoclonal T-cell population (by TCR gene rearrangement studies) → raises suspicion for MF even in "idiopathic" cases
• ⚠️ Alopecia mucinosa is NOT a primary cicatricial alopecia — the hair follicle is not replaced by true scar

Investigations

• Skin biopsy with H&E + mucin stains (Alcian blue, colloidal iron, PAS)
• Immunohistochemistry: CD4/CD8 ratio, atypical T-cell markers
• TCR gene rearrangement (PCR) — to exclude clonal lymphoma
• Full staging workup if MF suspected: PET-CT, bone marrow biopsy, peripheral blood flow cytometry

Treatment

• Spontaneous resolution possible (especially in children) — watchful waiting is appropriate
• Topical corticosteroids (mid-to-high potency)
• Intralesional corticosteroids (triamcinolone acetonide)
• Oral corticosteroids — for widespread/rapidly progressing disease
• Dapsone: anti-inflammatory; useful in some cases
• Indomethacin
• Minocycline: anti-inflammatory properties
• Isotretinoin
• Hydroxychloroquine
• Light therapy (NB-UVB) — especially for larger plaques

• Treatment targets the underlying lymphoma:
  • Narrowband UVB, PUVA
  • Topical mechlorethamine (nitrogen mustard)
  • Radiotherapy (local/total skin electron beam)
  • Systemic therapy: bexarotene, interferon-alfa, romidepsin, mogamulizumab
• Standard alopecia mucinosa treatments may also help symptomatically

Prognosis

• Idiopathic (child/adolescent): Excellent; spontaneous resolution with hair regrowth in 1–2 years
• Adult idiopathic: More persistent; requires monitoring to exclude MF
• Secondary (MF-associated): Depends on stage of lymphoma; folliculotropic MF has worse prognosis than classic patch-stage MF due to follicular depth limiting treatment penetration

• Are you asking for alopecia mucinosa alone (a more detailed/expanded answer than the 5-mark version I gave yesterday)?
• Or is this a list like "A) Alopecia mucinosa / B) [topic] / C) [topic]..." for a new set of answers?